A novel COL2A1 mutation (c.1888G>T(p.Gly630Cys)) in a Chinese family with Avascular necrosis of the femoral head

Abstract

Abstract Background: Familial avascular necrosis of the femoral head (ANFH) was a complex and complicated orthopedic disorder that cause changes in the structure of type II collagen due to a pathogenic mutation in the COL2A1 gene. With the damage to cartilage and bone, the disease gradually deteriorated into familial ANFH. The reports of familial ANFH were extremely rare. Besides, misdiagnosis and missed diagnosis are extremely likely to occur due to the difficulty of diagnosis. Case presentation: A 54-year-old woman developed soreness and pain in her right hip five months before admission without any apparent cause. The above symptoms suddenly worsened after four-month, and she was diagnosed with avascular necrosis of the femoral head (ANFH). The radiograph and MRI images (anteroposterior view) results of the pelvis and hip joints of the patient showed ANFH in stage II (based on the standard table of ARCO). whole-exome sequencing and analysis were conducted with the consent of family members. After Carrying out whole exon sequencing and analysis and selecting candidate gene mutations for ANFH in chr12. Then, we sequenced exonic regions of the type II collagen gene (COL2A1) from patients with inherited and sporadic forms of ANFH. The mutation in COL2A1 gene on chr12 was determined by analyzing and examining candidate genes. A C→A transition in COL2A1 gene was detected in II-7, III-11, III-13, IV-5 and IV-6 family members. This transition caused the replacement of glycine with cysteine in (Gly-X-Y)n region. Sanger sequencing was performed to verify the above mutation and the results are consistent with the above conclusion. Conclusions: This case was from China. Findings from imaging showed that there were significant differences between familial ANFH and general ANFH. These differences were most likely due to unique phenotypes resulting from pathogenic mutations in the COL2A1 gene. The result found that a new mutation type c.1888G>T(p.Gly630Cys) may cause significant distortion of Collagen Triple-Helix Structure, which had not been reported previously. This study revealed a novel and potential mutation leading to femoral head necrosis, which provides an imaging and molecular basis for the diagnosis and timely treatment in additional members of the family.